title: Affinity peptides protect transforming growth factor beta during encapsulation in poly(ethylene glycol) hydrogels.
abstract: Transforming growth factor beta (TGFβ(1)) influences a host of cellular fates, including proliferation, migration, and differentiation. Due to its short half-life and cross reactivity with a variety of cells, clinical application of TGFβ(1) may benefit from a localized delivery strategy. Photoencapsulation of proteins in polymeric matrices offers such an opportunity; however, the reactions forming polymer networks often result in lowered protein bioactivity. Here, PEG-based gels formed from the chain polymerization of acrylated monomers were studied as a model system for TGFβ(1) delivery. Concentrations of acrylate group ranging from 0 to 50 mM and photopolymerization conditions were systematically altered to study their effects on TGFβ(1) bioactivity. In addition, two peptide sequences, WSHW (K(D) = 8.20 nM) and KRIWFIPRSSWY (K(D) = 10.41 nM), that exhibit binding affinity for TGFβ(1) were introduced into the monomer solution prior to encapsulation to determine if affinity binders would increase the activity and release of the encapsulated growth factor. The addition of affinity peptides enhanced the bioactivity of TGFβ(1) in vitro from 1.3- to 2.9-fold, compared to hydrogels with no peptide. Further, increasing the concentration of affinity peptides by a factor of 100-10000 relative to the TGFβ(1) concentration increased fractional recovery of the protein from PEG hydrogels.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309-0424, United States.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: McCall
authors.forename: Chien-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
mesh_terms: D000595:Amino Acid Sequence; D001682:Biological Availability; D006207:Half-Life; D020100:Hydrogels; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols; D020349:Surface Plasmon Resonance; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D020100:Hydrogels; D010455:Peptides; D016212:Transforming Growth Factor beta; D011092:Polyethylene Glycols